Objective:To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined.Methods:Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted.Results:The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation ( P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.216). Conclusions:The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

OBJECTIVE To study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis （AD） mice，and to explore the mechanism of action. METHODS Fifty mice were randomly divided into 5 groups，i.e. normal control group （group A），model group （group B），dexamethasone intervention group （positive control，group C），H. rhamnoides oil intervention group （group D），dexamethasone+H. rhamnoides oil intervention group （group E），with 10 mice in each group. Except for group A，other groups were given 2，4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment，groups C，D and E were given dexamethasone （1.5 mg/kg） and/or H. rhamnoides oil （10 mL/kg） intragastrically，once a day，for 28 consecutive days. After the last medication，the pathomorphological changes of ear tissue were observed by 节作用。E-mail：57667478@qq.com HE staining； the serum levels of immunoglobulin E （IgE） and interleukin 4 （IL-4） were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α （GRα） and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein，GRβ protein，and protein kinase B （AKT）/ribosomal protein S6 kinase 1，S6K1 （S6K1） signaling pathway-related proteins were determined by Western blot assay. RESULTS Compared with group B，the skin inflammation in the left ear of the mice was significantly reduced in groups C，D and E，the serum levels of IgE and IL-4 were decreased significantly in groups D and E （P＜ 0.05），while the number of GRα positive cells and GRα protein expression were increased significantly （P＜0.05）； the protein levels of G protein inhibitory subunit 1 （Gαi1），Gαi3，phosphorylated S6K1 （p-S6K1） and phosphorylated AKT （p-AKT） were decreased significantly （P＜0.05）； the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E（P＜0.05）. Compared with group C，the skin inflammation in the left ear of the mice was almost clear away in group E，the serum levels of IgE and IL-4 were decreased significantly （P＜0.05）； the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E （P＜0.05）； the protein levels of GRβ，Gαi1，p-S6K1 and p-AKT were all decreased significantly in groups D and E（P＜0.05）； and protein level of Gαi3 was decreased significantly in group E （P＜0.05）. CONCLUSIONS H. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice，which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.

Objective:To investigate the experience and results of the modified lateral prostate capsule sparing robot-assisted radical cystectomy-orthotopic ileal neobladder (LPCS-RARC-OIN).Methods:From December 2018 to November 2020, 19 patients received LPCS-RARC-OIN by a single surgeon in Sun Yat-sen Memorial Hospital, Sun Yat-sen University. LPCS-RARC-OIN was performed on male patients with high-risk non-muscle-invasive bladder cancer or muscle-invasive bladder cancer cT 2N 0M 0 without tumour in the bladder neck or urethra, and prostate cancer was ruled out by MRI and serum PSA<2.5ng/ml. The average age was 57.6 years, the average IIEF-5 score was 20.4. Separating the prostatic adenoma and the lateral prostate capsule from the base to the apex of the prostate, and retaining the lateral prostate surgical capsule or lateral prostate capsule about 1-2mm thickness. Patients were followed up and urinary function, sexual function and oncological outcomes were recorded. Results:All 19 operations were finished successfully. The average operation time was 279.9 (225-345) min and average estimated blood loss was 88.9 (30-200) ml. The average postoperative hospital stays was 15.8 (9 -23) days. The average lymph node yields was 23.3 (11-42). All surgical margins were negative and no incidental prostate cancer was found. 2 weeks, 1 month, 3 months and 6 months after catheter removal, the daytime and nighttime continence were 42.1% (8/19)and 36.8% (7/19), 63.2% (12/19)and 63.2% (12/19), 78.9% (15/19) and 73.7% (14/19), 94.7% (18/19) and 89.5% (17/19), respectively. 3 months and 6 months after operation, the average IIEF-5 score was 7.2 and 10.1 points respectively. The average follow-up was 10.6 months (5.4-26.1 months)and no recurrence or distant metastasis was found in this study.Conclusions:LPCS-RARC-OIN could improve the urinary and sexual function in selected patients. However, the long-term follow up is needed for functional and oncological outcomes.

Objective: To investigate the effect of miR-135a on the malignant biological behaviors of human laryngeal carcinoma epithelial Hep-2 cells and its sensitivity to oxaliplatin. Methods: Samples of laryngeal carcinoma tissues and para-cancerous tissues were collected from 10 patients who underwent laryngectomy in Nanyang Hospital Affiliated to Zhengzhou University-Nanyang City Center Hospital from January 2018 to June 2018. The expression of miR-135a in laryngeal carcinoma tissues and Hep-2 cells was detected by qPCR.After being transfected with miR-135 inhibitor, cell proliferation viability of Hep-2 cells was measured by CCK-8 assay, cell colony formation ability was detected by colony formation assay, and cell proliferation invasion and migration abilities were detected by Transwell analysis, and the expression of SOX2 protein in Hep-2 cells was detected by WB. Hep-2 cells transfected with miR-135 inhibitor were further treated with various concentrations (0.5, 1.0, 1.5 and 2.0 μmol/L) of oxaliplatin, and the cell proliferation viability was detected by CCK-8 while cell apoptosis was detected by Annexin-V-FITC/PI double staining flow cytometry. miR-135a inhibitor plasmid, control pcDNA empty vector (SOX2-Con) plasmid, and pcDNA-SOX2 (SOX2-OE) plasmid were transfected into Hep-2 cells to construct the miR-135a inhibitor+SOX2-Con group and miR-135a inhibitor+SOX2-OE group, and the cell viability, cell colony formation ability, cell invasion and migration ability in two groups were detected. Results: Compared with para-cancerous tissues, miR135a expression in laryngeal cancer tissues was significantly increased (P<0.01). Compared with normal NHP cells, miR-135a expression in Hep-2 cells was significantly increased (P<0.01). miR-135a inhibitor significantly reduced the expression level of miR-135a in Hep-2 cells (P<0.01). miR-135a knockdown significantly reduced the cell proliferation viability, cell colony number, migration, invasion and SOX2 expression in Hep-2 cells (all P <0.01), but significantly enhanced the sensitivity of Hep-2 cells to oxaliplatin (P<0.01). Compared with miR-135a inhibitor+SOX2-Con group, the cell proliferation viability, cell colony number, migration and invasion of Hep-2 cells in miR-135a inhibitor+SOX2-OE group were significantly increased (P<0.01); Meanwhile, the cells of the 2 groups were treated with different concentrations of oxaliplatin, and the results of CCK-8 assay showed that, compared with the miR-135a inhibitor+ SOX2-Con group, the cell proliferation viability of Hep-2 cells in miR-135a inhibitor+SOX2-OE group was significantly increased (P< 0.01). Conclusion: miR-135a knockdown inhibits the malignant biological behaviors and promotes oxaliplatin-sensitivity of Hep-2 cells possibly by inhibiting the expression of the transcription factor SOX2.

OBJECTIVETo investigate the changes of aldehyde dehydrogenase 2 (ALDH2) expression in H O inducedcardiomyocytes oxidative stress injury.

METHODSCultured H9C2 cardiomyocytes were exposed to H O -inducedoxidative stress and the effects of the ALDH2 agonist Alda-1 and ALDH2 inhibitor Daidzin were tested on the stress level ofthe exposed cells. MTT colorimetric assay was used to assess the cell viability after the treatments. The oxidative stress level inthe myocardial cells was detected using DHE fluorescence staining, and the activity and protein level of ALDH2 were detectedwith spectrophotometry and Western blotting.

RESULTSCompared with normal control cells, Alda-1 treatment did notsignificantly affect the cell viability, oxidative stress level, or ALDH2 activity and protein level. H O exposure significantlylowered the cell activity and ALDH2 activity and protein expression and increased the oxidative stress level; Alda-1 treatmentobvious antagonized the effects of H O . Blocking ALDH2 with Daidzin produced similar effects to H O exposure on theviability, oxidative stress level, and ALDH2 activity and expression in the myocardial cells.

CONCLUSIONSH O exposure lowersthe activity and reduces the protein expression of ALDH2 in cardiomyocyte H9C2 cells, and activation of ALDH2 can alleviateH O -induced oxidative stress in the cells.

Objective To compare split-cuff nipple and direct ureteroileal anastomosis during ureteroileal anastomosis.Methods Between December,2014 and March,2017,a prospective randomized study was conducted on 70 patients who underwent radical cystectomy and urinary diversion.In every patient,both ureters were randomized to be implanted using an antireflux,split-cuff nipple technique (group A) or a reflux,direct technique (group B).After pelvic lymph node dissection and radical cystectomy,a Mshape orthotopic ileal neobladder was constructed and two ureters were implanted with single-J tubes placed for 10-12 days.For split-cuff nipple technique,a 0.5 cm longitudinal incision in the ureter was made,and the ureteral wall was turned back on itself,construction a nipple.The cuff was stabilized at the corners with sutures.The ureter was then placed into the bowel with 0.5 cm nipple.The ureter was sutured to the full thickness of the bowel wall with interrupted 4-0 PDS.For direct technique,a 0.5 cm incision in the ureter was made,the full thickness of the ureter was sewn to the mucosa of the bowel.Results 70 patients were enrolled in the study,63 males and 7 females,(62.5 ± 10.4) years old.Over a median follow-up of 13.2 months,one patients had bilateral anastomosis stricture 3 months after operation,1 patient in group A had stricture 6 months after operation,2 patients in group B had stricture 6 and 12 months after operation,respectively.Six patients (8.6％) in group A found reflux compared with 21 patients (30.0％) in group B (P =0.004).The reflux pressure was (23.5 ± 9.0) cmH2O and (15.5 ± 4.9) cmH2O in group A and group B (P =0.042),respectively.The GFR of group A was (38.1 ± 7.6) ml/min compared with (38.6 ± 12.9) ml/min in group B at 12 months after operation.One patient in group A and four patients in group B had acute nephropyelitis.Four patients in group A had renal stones formation compared with 1 patients in group B.The time of anastomosis was (8.8 ± 3.5) minutes and (6.7 ± 1.5) minutes (P =0.037) for group A and group B,respectively.The patients in both groups had no urine leakage.Conclusion Compared with direct technique,split-cuff nipple technique had lower reflux rate,higher antireflux pressure and longer anastomosis time than direct technique.

Objective To evaluate the therapeutic effect of Xiaoqinglong decoction combined with standard treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods A total of 60 patients with acute exacerbation of COPD were enrolled and randomly divided into a standard treatment group and a combined treatment group, 30 in each group. The standard treatment group received standard therapy and the combined treatment group receivedXiao Qing Long decoction combined with standard treatment. The forced vital capacity (FVC), forced expiratory volume in first second (FEV1), FEV1/FVC were detected using a pulmonary function tester. The partial pressure of arterial oxygen (PaO2), carbon dioxide (PaCO2) were evaluated.Results After the treatment, the FVC (1.94 ± 0.26 Lvs. 1.55 ± 0.33 L;t=-2.201, P<0.05), FEV1 (1.34 ± 0.24 Lvs. 0.99 ± 0.25 L;t=-6.004,P<0.05), and PaO2 (86.12 ± 13.26 mmHgvs. 80.02 ± 12.75 mmHg;t=-14.158,P<0.05) in the combined treatment group were significantly higher than those in the standard treatment group. The total effective rate in the combined treatment group was significantly higher than that in the standard treatment group (86.7%vs.70.0%;χ2=2.095,P=0.036).Conclusions Xiaoqinglong decoction combined with standard treatment can improve symptom, sign, arterial blood gas and the pulmonary function in patients with acute exacerbation of COPD, and its efficiency is superior to standard therapy alone.

Objective To observe the in vitro influence of recombinant human B7-H4 protein on the cell proliferation cycle, apoptosis and cytokine secretion of peripheral blood activated T lymphocytes in cervical cancer patients.Methods After 48 h co-culture of peripheral blood T lymphocytes in 1 5 cases of cervical cancer with B7-H4 48 h,T lymphocytes′cell proliferation cycle, apoptosis and T lymphocytes subtypes changes were detected by FCM;the cytokines concentration in the culture supernatant was tested by ELISA array.Results After 48 h co-culture of peripheral blood T lymphocytes with B7-H4 48hs,G1,G2 and S phase of T cells accounted for 90.59%,8.55% and 0.87% respectively,which of the blank group were 92.83%,6.09% and 1.13% respec-tively;the Ki67 positive rates of CD4 + T and CD8 + T cells in the B7-H4 group were 2.13%±0.13% and 1.03%±1.33% respec-tively,which of the blank group were 2.74% ±0.98% and 1.71% ± 1.32% respectively;the proportion of CD4 + T and CD8 + T cells accounting for T cells in the B7-H4 group was decreased compared with the blank group,but the ratio of CD4 + T/CD8 + T and the proportion of CD4 + CD25 + Foxp3 + T cells were increased,in addition,the TGF-β1 secretion;concentration in the co-culture su-pernatant in the B7-H4 group was (259.25±32.78)pg/mL,which was higher than (202.75 ±20.1 7)pg/mL in the blank group. B7-H4 had no significant influence on the peripheral blood activated T cells apoptosis.Conclusion B7-H4 block the peripheral blood activated T cells at G2 phase,the S phase cells are obviously decreased;B7-H4 inhibits the cellular proliferation of CD4 + T and CD8 + cells,but may have the promoting effect on Foxp3 + T proliferation and TGF-β1 secretion;B7-H4 has no significant influ-ence on T cell apoptosis.B7-H4 plays a role in depressing anti-tumor T cell immune response of cervical cancer and may become a potential target of cervical cancer immunotherapy.

Objective To evaluate the detection rate of multi-slice spiral CT (MSCT)signs and the clinical value of multi-planar reconstruction (MPR)in T1a and T1b peripheral lung cancer patients.Methods Eighty-seven cases with peripheral lung cancer proved by pathology were collected.The cases were divided into T1a and T1b group based on the TNM classification.The MSCT and MPR images were compared between the two groups.Results (1)Detection rate of the deep sublobe sign,spinous process sign, short spiculated sign,pleural indentation sign,vascular convergence sign,multi-nodule accumulation sign,vacuole sign and air bron-chogram sign,were 1 1.4%,20.0%,31.4%,60.0%,25.7%,45.7%,42.9% in T1a group and 42.3%,36.5%,57.7%, 80.8%,5 1.9%,25.0%,21.2% in T1b group,respectively.The difference were all statistically significant (P < 0.05)between T1a and T1b group except that of the spiculated sign (P = 0.098).(2)The detection rate of the sublobe sign,spinous process sign, spiculated sign,pleural indentation sign and vascular convergence sign were higher on MPR images than on axial thin-slice images in both T1a and T1b group.Conclusion The detection rate of the tumor-lung interface’s signs are lower in T1a than in T1b,the detec-tion rate of internal structure signs of the tumor are higher in T1a than in T1b in peripheral lung cancer patients.MPR has important value in early diagnosis of peripheral lung cancer.